The accuracy of ADC measurements in liver is improved by a tailored and computationally efficient local-rigid registration algorithm

This study describes post-processing methodologies to reduce the effects of physiological motion in measurements of apparent diffusion coefficient (ADC) in the liver. The aims of the study are to improve the accuracy of ADC measurements in liver disease to support quantitative clinical characterisation and reduce the number of patients required for sequential studies of disease progression and therapeutic effects. Two motion correction methods are compared, one based on non-rigid registration (NRA) using freely available open source algorithms and the other a local-rigid registration (LRA) specifically designed for use with diffusion weighted magnetic resonance (DW-MR) data. Performance of these methods is evaluated using metrics computed from regional ADC histograms on abdominal image slices from healthy volunteers. While the non-rigid registration method has the advantages of being applicable on the whole volume and in a fully automatic fashion, the local-rigid registration method is faster while maintaining the integrity of the biological structures essential for analysis of tissue heterogeneity. Our findings also indicate that the averaging commonly applied to DW-MR images as part of the acquisition protocol should be avoided if possible

Examining the Overlap Between ADHD and Autism Spectrum Disorder (ASD) Using Candidate Endophenotypes of ADHD

Objective: Recent discussions of aetiological overlap between ADHD and Autism Spectrum Disorder (ASD) require comparative studying of these disorders. Method: We examined performance of ASD patients with (ASD+) and without (ASD-) comorbid ADHD, ADHD patients, and controls for selected putative endophenotypes of ADHD: Intrasubject Variability (ISV) of reaction times, working memory (WM), inhibition, and temporal processing. Results: We found that patients with ADHD or ASD+, but not ASD-, had elevated ISV across the entire task battery and temporal processing deficits, and that none of the groups were impaired in WM or inhibition. High levels of ISV and generally poor performance in ASD+ patients were only partially due to additive effects of the pure disorders. Conclusion: Overall, we conclude that, within our limited but heterogeneous task battery, ISV and temporal processing deficits are most sensitive to ADHD symptomatology and that controlling for ADHD comorbidity is mandatory when assessing ISV in autism

High performance methylated DNA markers for detection of colon adenocarcinoma

BACKGROUND: Colon cancer (CC) is treatable if detected in its early stages. Improved CC detection assays that are highly sensitive, specific, and available at point of care are needed. In this study, we systematically selected and tested methylated markers that demonstrate high sensitivity and specificity for detection of CC in tissue and circulating cell-free DNA. METHODS: Hierarchical analysis of 22 candidate CpG loci was conducted using The Cancer Genome Atlas (TCGA) COAD 450K HumanMethylation database. Methylation of 13 loci was analyzed using quantitative multiplex methylation-specific PCR (QM-MSP) in a training set of fresh frozen colon tissues (N = 53). Hypermethylated markers were identified that were highest in cancer and lowest in normal colon tissue using the 75th percentile in Mann–Whitney analyses and the receiver operating characteristic (ROC) statistic. The cumulative methylation status of the marker panel was assayed in an independent test set of fresh frozen colon tissues (N = 52) using conditions defined and locked in the training set. A minimal marker panel of 6 genes was defined based on ROC area under the curve (AUC). Plasma samples (N = 20 colorectal cancers, stage IV and N = 20 normal) were tested by cMethDNA assay to evaluate marker performance in liquid biopsy. RESULTS: In the test set of samples, compared to normal tissue, a 6-gene panel showed 100% sensitivity and 90% specificity for detection of CC, and an AUC of 1.00 (95% CI 1.00, 1.00). In stage IV colorectal cancer plasma versus normal, an 8-gene panel showed 95% sensitivity, 100% specificity, and an AUC of 0.996 (95% CI 0.986, 1.00) while a 5-gene subset showed 100% sensitivity, 100% specificity, and an AUC of 1.00 (95% CI 1.00, 1.00), highly concordant with our observations in tissue. CONCLUSIONS: We identified high performance methylated DNA marker panels for detection of CC. This knowledge has set the stage for development and implementation of novel, automated, self-contained CC detection assays in tissue and blood which can expeditiously and accurately detect colon cancer in both developed and underdeveloped regions of the world, enabling optimal use of limited resources in low- and middle-income countries. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s13148-021-01206-2

Resonant nonlinear optics of backward waves in negative-index metamaterials

The extraordinary properties of resonant four-wave mixing of backward waves in doped negative-index materials are investigated. The feasibility of independent engineering of negative refractive index and nonlinear optical response as well as quantum control of the nonlinear propagation process in such composites is shown due to the coherent energy transfer from the control to the signal field. Laser-induced transparency, quantum switching, frequency-tunable narrow-band filtering, amplification, and realizing a miniature mirrorless optical parametric generator of the entangled backward and ordinary waves are among the possible applications of the investigated processes.Comment: 10 pages, 9 figure

Success or failure in knowledge management systems: a universal issue

This paper takes a sociotechnical viewpoint of knowledge management system (KMS) implementation in organizations considering issues such as stakeholder disenfranchisement, lack of communication, and the low involvement of key personnel in system design asking whether KMS designers could learn from applying sociotechnical principles to their systems. The paper discusses design elements drawn from the sociotechnical principles essential for the success of IS and makes recommendations to increase the success of KMS in organizations. It also provides guidelines derived from Clegg’s Principles (2000) for KMS designers to enhance their designs. Our data comes from the application of a plurality of analysis methods on a large comprehensive global survey conducted from 2007 to 2011 of 1034 participants from 76 countries. The survey covers a variety of organizations of all types and sizes from a comprehensive selection of economic sectors and industries. Our results showed that users were not satisfied with the information and knowledge systems that they were being offered. In addition to multiple technology and usability issues, there were human and organisational barriers that prevented the systems from being used to their full potential. We recommend that users of KMS are integrated into the design team so that these usability and other barriers can be addressed during the feasibility stage as well as the actual design and implementation phases

Automated Assessment of T2-Weighted MRI to Differentiate Malignant and Benign Primary Solid Liver Lesions in Noncirrhotic Livers Using Radiomics

Rationale and Objectives: Distinguishing malignant from benign liver lesions based on magnetic resonance imaging (MRI) is an important but often challenging task, especially in noncirrhotic livers. We developed and externally validated a radiomics model to quantitatively assess T2-weighted MRI to distinguish the most common malignant and benign primary solid liver lesions in noncirrhotic livers. Materials and Methods: Data sets were retrospectively collected from three tertiary referral centers (A, B, and C) between 2002 and 2018. Patients with malignant (hepatocellular carcinoma and intrahepatic cholangiocarcinoma) and benign (hepatocellular adenoma and focal nodular hyperplasia) lesions were included. A radiomics model based on T2-weighted MRI was developed in data set A using a combination of machine learning approaches. The model was internally evaluated on data set A through cross-validation, externally validated on data sets B and C, and compared to visual scoring of two experienced abdominal radiologists on data set C. Results: The overall data set included 486 patients (A: 187, B: 98, and C: 201). The radiomics model had a mean area under the curve (AUC) of 0.78 upon internal validation on data set A and a similar AUC in external validation (B: 0.74 and C: 0.76). In data set C, the two radiologists showed moderate agreement (Cohen's κ: 0.61) and achieved AUCs of 0.86 and 0.82. Conclusion: Our T2-weighted MRI radiomics model shows potential for distinguishing malignant from benign primary solid liver lesions. External validation indicated that the model is generalizable despite substantial MRI acquisition protocol differences. Pending further optimization and generalization, this model may aid radiologists in improving the diagnostic workup of patients with liver lesions.</p

Population dynamics in compressible flows

Organisms often grow, migrate and compete in liquid environments, as well as on solid surfaces. However, relatively little is known about what happens when competing species are mixed and compressed by fluid turbulence. In these lectures we review our recent work on population dynamics and population genetics in compressible velocity fields of one and two dimensions. We discuss why compressible turbulence is relevant for population dynamics in the ocean and we consider cases both where the velocity field is turbulent and when it is static. Furthermore, we investigate populations in terms of a continuos density field and when the populations are treated via discrete particles. In the last case we focus on the competition and fixation of one species compared to anotherComment: 16 pages, talk delivered at the Geilo Winter School 201

SRSF2 Mutations in Uveal Melanoma: A Preference for In-Frame Deletions?

Background: Uveal melanoma (UM) is the most common primary ocular malignancy in adults in the Western world. UM with a mutation in SF3B1, a spliceosome gene, is characterized by three or more structural changes of chromosome 1, 6, 8, 9, or 11. Also UM without a mutation in SF3B1 harbors similar chromosomal aberrations. Since, in addition to SF3B1, mutations in U2AF1 and SRSF2 have also been observed in hematological malignancies, UM without a SF3B1 mutation—but with the characteristic chromosomal pattern—might harbor mutations in one of these genes. Methods: 42 UMs were selected based on their chromosomal profile and wildtype SF3B1 status. Sanger sequencing covering the U2AF1 (exon 2 and 7) hotspots and SRSF2 (exon 1 and 2) was performed on DNA extracted from tumor tissue. Data of three UM with an SRSF2 mutation was extracted from the The Cancer Genome Atlas (TCGA). Results: Heterozygous in-frame SRSF2 deletions affecting amino acids 92–100 were detected in two UMs (5%) of 42 selected tumors and in three TGCA UM specimens. Both the UM with an SRSF2 mutation from our cohort and the UM samples from the TCGA showed more than four structural chromosomal aberrations including (partial) gain of chromosome 6 and 8, although in two TCGA UMs monosomy 3 was observed. Conclusions: Whereas in myelodysplastic syndrome predominantly missense SRSF2 mutations are described, the observed SRSF2 mutations in UM are all in-frame deletions of 8–9 amino acids. This suggests that the R625 missense SF3B1 mutations and SRSF2 mutations in UM are different compared to the spliceosome gene mutations in hematological cancers, and probably target a different, as yet unknown, set of genes involved in uv

Boltzmann limit and quasifreeness for a homogenous Fermi gas in a weakly disordered random medium

We discuss some basic aspects of the dynamics of a homogenous Fermi gas in a weak random potential, under negligence of the particle pair interactions. We derive the kinetic scaling limit for the momentum distribution function with a translation invariant initial state and prove that it is determined by a linear Boltzmann equation. Moreover, we prove that if the initial state is quasifree, then the time evolved state, averaged over the randomness, has a quasifree kinetic limit. We show that the momentum distributions determined by the Gibbs states of a free fermion field are stationary solutions of the linear Boltzmann equation; this includes the limit of zero temperature.Comment: AMS Latex, 26 pages. 2 figures. References added, minor typos correcte

Chromosomal rearrangements in uveal melanoma: Chromothripsis

Uveal melanoma (UM) is the most common primary intraocular malignancy in the Western world. Recurrent mutations in GNAQ, GNA11, CYSLTR2, PLCB4, BAP1, EIF1AX, and SF3B1 are described as well as non-random chromosomal aberrations. Chromothripsis is a rare event in which chromosomes are shattered and rearranged and has been reported in a variety of cancers including UM. SNP arrays of 249 UM from patients who underwent enucleation, biopsy or endoresection were reviewed for the presence of chromothripsis. Chromothripsis was defined as ten or more breakpoints per chromosome involved. Genetic analysis of GNAQ, GNA11, BAP1, SF3B1, and EIF1AX was conducted using Sanger and next-generation sequencing. In addition, immunohistochemistry for BAP1 was performed. Chromothripsis was detected in 7 out of 249 tumors and the affected chromosomes were chromosomes 3, 5, 6, 8, 12, and 13. The mean total of fragments per chromosome was 39.8 (range 12-116). In 1 UM, chromothripsis was present in 2 different chromosomes. GNAQ, GNA11 or CYSLTR2 mutations were present in 6 of these tumors and 5 tumors harbored a BAP1 mutation and/or lacked BAP1 protein expression by immunohistochemistry. Four of these tumors metastasized and for the fifth only short follow-up data are available. One of these metastatic tumors harbored an SF3B1 mutation. No EIF1AX mutations were detected in any of the tumors. To conclude, chromothripsis is a rare event in UM, occurring in 2.8% of samples and without significant association with mutations in any of the common UM driver genes